scholarly journals Ubiquitination is essential for recovery of cellular activities following heat shock

2021 ◽  
Author(s):  
Brian A. Maxwell ◽  
Youngdae Gwon ◽  
Ashutosh Mishra ◽  
Junmin Peng ◽  
Ke Zhang ◽  
...  
Keyword(s):  
Heat Stress ◽  
Heat Shock ◽  
Nucleocytoplasmic Transport ◽  
Stress Granule ◽  
Misfolded Proteins ◽  
Eukaryotic Cells ◽  
Granule Formation ◽  
Cellular Processes ◽  
Different Types ◽  
Global Increase

AbstractEukaryotic cells respond to stress via adaptive programs that include reversible shutdown of key cellular processes, the formation of stress granules, and a global increase in ubiquitination. The primary function of this ubiquitination is generally considered to be tagging damaged or misfolded proteins for degradation. Here we show that different types of stress generate distinct ubiquitination patterns. For heat stress, ubiquitination correlates with cellular activities that are downregulated during stress, including nucleocytoplasmic transport and translation, as well as with stress granule constituents. Ubiquitination is not required for the shutdown of these processes or for stress granule formation, but is essential for resumption of cellular activities and for stress granule disassembly. These findings indicate that stress-induced ubiquitination primes the cell for recovery following heat stress.One Sentence SummaryStress-induced ubiquitination is essential for recovery of cellular activities following heat stress.

scholarly journals Ubiquitination is essential for recovery of cellular activities after heat shock

Science ◽  
2021 ◽  
Vol 372 (6549) ◽  
pp. eabc3593
Author(s):  
Brian A. Maxwell ◽  
Youngdae Gwon ◽  
Ashutosh Mishra ◽  
Junmin Peng ◽  
Haruko Nakamura ◽  
...  
Keyword(s):  
Heat Stress ◽  
Cultured Cells ◽  
Nucleocytoplasmic Transport ◽  
Stress Granule ◽  
Eukaryotic Cells ◽  
Granule Formation ◽  
Cellular Processes ◽  
Specific Proteins ◽  
Global Increase ◽  
As Stress

Eukaryotic cells respond to stress through adaptive programs that include reversible shutdown of key cellular processes, the formation of stress granules, and a global increase in ubiquitination. The primary function of this ubiquitination is thought to be for tagging damaged or misfolded proteins for degradation. Here, working in mammalian cultured cells, we found that different stresses elicited distinct ubiquitination patterns. For heat stress, ubiquitination targeted specific proteins associated with cellular activities that are down-regulated during stress, including nucleocytoplasmic transport and translation, as well as stress granule constituents. Ubiquitination was not required for the shutdown of these processes or for stress granule formation but was essential for the resumption of cellular activities and for stress granule disassembly. Thus, stress-induced ubiquitination primes the cell for recovery after heat stress.

scholarly journals Disruption of Stress Granule Formation by the Multifunctional Cricket Paralysis Virus 1A Protein

2016 ◽  
Vol 91 (5) ◽  
Author(s):  
Anthony Khong ◽  
Craig H. Kerr ◽  
Clarence H. L. Yeung ◽  
Kathleen Keatings ◽  
Arabinda Nayak ◽  
...  
Keyword(s):  
Virus Infection ◽  
Stress Granule ◽  
Granule Formation ◽  
Viral Translation ◽  
Content Type ◽  
Cellular Processes ◽  
Cellular Environment ◽  
Viral Yield ◽  
Infected Cells ◽  
Paralysis Virus

ABSTRACT Stress granules (SGs) are cytosolic ribonucleoprotein aggregates that are induced during cellular stress. Several viruses modulate SG formation, suggesting that SGs have an impact on virus infection. However, the mechanisms and impact of modulating SG assembly in infected cells are not completely understood. In this study, we identify the dicistrovirus cricket paralysis virus 1A (CrPV-1A) protein that functions to inhibit SG assembly during infection. Moreover, besides inhibiting RNA interference, CrPV-1A also inhibits host transcription, which indirectly modulates SG assembly. Thus, CrPV-1A is a multifunctional protein. We identify a key R146A residue that is responsible for these effects, and mutant CrPV(R146A) virus infection is attenuated in Drosophila melanogaster S2 cells and adult fruit flies and results in increased SG formation. Treatment of CrPV(R146A)-infected cells with actinomycin D, which represses transcription, restores SG assembly suppression and viral yield. In summary, CrPV-1A modulates several cellular processes to generate a cellular environment that promotes viral translation and replication. IMPORTANCE RNA viruses encode a limited set of viral proteins to modulate an array of cellular processes in order to facilitate viral replication and inhibit antiviral defenses. In this study, we identified a viral protein, called CrPV-1A, within the dicistrovirus cricket paralysis virus that can inhibit host transcription, modulate viral translation, and block a cellular process called stress granule assembly. We also identified a specific amino acid within CrPV-1A that is important for these cellular processes and that mutant viruses containing mutations of CrPV-1A attenuate virus infection. We also demonstrate that the CrPV-1A protein can also modulate cellular processes in human cells, suggesting that the mode of action of CrPV-1A is conserved. We propose that CrPV-1A is a multifunctional, versatile protein that creates a cellular environment in virus-infected cells that permits productive virus infection.

scholarly journals Stable Formation of Compositionally Unique Stress Granules in Virus-Infected Cells

2009 ◽  
Vol 84 (7) ◽  
pp. 3654-3665 ◽  
Author(s):  
Joanna Piotrowska ◽  
Spencer J. Hansen ◽  
Nogi Park ◽  
Katarzyna Jamka ◽  
Peter Sarnow ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heat Shock ◽  
Viral Infections ◽  
De Novo ◽  
Stress Granules ◽  
Stress Granule ◽  
Initiation Factor ◽  
Granule Formation ◽  
Infected Cells ◽  
Positive Strand Rna

ABSTRACT Stress granules are sites of mRNA storage formed in response to a variety of stresses, including viral infections. Here, the mechanisms and consequences of stress granule formation during poliovirus infection were examined. The results indicate that stress granules containing T-cell-restricted intracellular antigen 1 (TIA-1) and mRNA are stably constituted in infected cells despite lacking intact RasGAP SH3-domain binding protein 1 (G3BP) and eukaryotic initiation factor 4G. Fluorescent in situ hybridization revealed that stress granules in infected cells do not contain significant amounts of viral positive-strand RNA. Infection does not prevent stress granule formation in response to heat shock, indicating that poliovirus does not block de novo stress granule formation. A mutant TIA-1 protein that prevents stress granule formation during oxidative stress also prevents formation in infected cells. However, stress granule formation during infection is more dependent upon ongoing transcription than is formation during oxidative stress or heat shock. Furthermore, Sam68 is recruited to stress granules in infected cells but not to stress granules formed in response to oxidative stress or heat shock. These results demonstrate that stress granule formation in poliovirus-infected cells utilizes a transcription-dependent pathway that results in the appearance of stable, compositionally unique stress granules.

Biomedical analysis of exosomes using biosensing methods: recent progress

2020 ◽  
Vol 12 (22) ◽  
pp. 2795-2811 ◽  
Author(s):  
Houman Kholafazad Kordasht ◽  
Mohammad Hasanzadeh
Keyword(s):  
Extracellular Vesicles ◽  
Intercellular Communication ◽  
Recent Progress ◽  
Eukaryotic Cells ◽  
Biomedical Analysis ◽  
Cellular Processes ◽  
Different Types ◽  
Membrane Bound

Exosomes are membrane-bound extracellular vesicles (EVs) that are produced in the endosomal compartments of most eukaryotic cells; they play important roles in intercellular communication in diverse cellular processes and transmit different types of biomolecules.

scholarly journals Inhibition of HSF1 and SAFB Granule Formation Enhances Apoptosis Induced by Heat Stress

2021 ◽  
Vol 22 (9) ◽  
pp. 4982
Author(s):  
Kazunori Watanabe ◽  
Takashi Ohtsuki
Keyword(s):  
Heat Stress ◽  
Heat Shock ◽  
Thermal Resistance ◽  
Resistance Mechanisms ◽  
Stress Recovery ◽  
Granule Formation ◽  
Induced Apoptosis ◽  
Shock Proteins ◽  
Transcription Factor 1 ◽  
Attachment Factor

Stress resistance mechanisms include upregulation of heat shock proteins (HSPs) and formation of granules. Stress-induced granules are classified into stress granules and nuclear stress bodies (nSBs). The present study examined the involvement of nSB formation in thermal resistance. We used chemical compounds that inhibit heat shock transcription factor 1 (HSF1) and scaffold attachment factor B (SAFB) granule formation and determined their effect on granule formation and HSP expression in HeLa cells. We found that formation of HSF1 and SAFB granules was inhibited by 2,5-hexanediol. We also found that suppression of HSF1 and SAFB granule formation enhanced heat stress-induced apoptosis. In addition, the upregulation of HSP27 and HSP70 during heat stress recovery was suppressed by 2,5-hexanediol. Our results suggested that the formation of HSF1 and SAFB granules was likely to be involved in the upregulation of HSP27 and HSP70 during heat stress recovery. Thus, the formation of HSF1 and SAFB granules was involved in thermal resistance.

scholarly journals The UBAP2L ortholog PQN-59 contributes to stress granule assembly and development in C. elegans

2021 ◽  
Author(s):  
Simona Abbatemarco ◽  
Alexandra Bondaz ◽  
Françoise Schwager ◽  
Jing Wang ◽  
Christopher M Hammell ◽  
...  
Keyword(s):  
Stress Granules ◽  
Stress Granule ◽  
Eukaryotic Cells ◽  
Stress Exposure ◽  
Exact Role ◽  
Granule Formation ◽  
Protective Function ◽  
C Elegans ◽  
Ribonucleoprotein Complexes ◽  
Higher Sensitivity

When exposed to stressful conditions, eukaryotic cells respond by inducing the formation of cytoplasmic ribonucleoprotein complexes called stress granules. Stress granules are thought to have a protective function but their exact role is still unclear. Here we use C. elegans to study two proteins that have been shown to be important for stress granule assembly in human cells: PQN-59, the ortholog of human UBAP2L, and GTBP-1, the ortholog of the human G3BP1 and G3BP2 proteins. Both proteins fall into stress granules in the embryo and in the germline when C. elegans is exposed to stressful conditions. None of the two proteins is essential for the assembly of stress induced granules, but the granules formed in absence of PQN-59 or GTBP-1 are less numerous and dissolve faster than the ones formed in control embryos. Despite these differences, pqn-59 or gtbp-1 mutant embryos do not show a higher sensitivity to stress than control embryos. pqn-59 mutants display reduced progeny and a high percentage of embryonic lethality, phenotypes that are not dependent on stress exposure and that are not shared with gtbp-1 mutants. Our data indicate that both GTBP-1 and PQN-59 contribute to stress granule formation but that PQN-59 is, in addition, required for C. elegans development.

scholarly journals Discovery of a nucleocytoplasmic O-mannose glycoproteome in yeast

2015 ◽  
Vol 112 (51) ◽  
pp. 15648-15653 ◽  
Author(s):  
Adnan Halim ◽  
Ida Signe Bohse Larsen ◽  
Patrick Neubert ◽  
Hiren Jitendra Joshi ◽  
Bent Larsen Petersen ◽  
...  
Keyword(s):  
Cell Lines ◽  
Human Cell ◽  
Large Family ◽  
Eukaryotic Cells ◽  
Human Cell Lines ◽  
Hexosamine Biosynthetic Pathway ◽  
Cellular Processes ◽  
Different Types ◽  
Nucleocytoplasmic Proteins ◽  
Enzymatic Machinery

Dynamic cycling of N-Acetylglucosamine (GlcNAc) on serine and threonine residues (O-GlcNAcylation) is an essential process in all eukaryotic cells except yeast, including Saccharomyces cerevisiae and Schizosaccharomyces pombe. O-GlcNAcylation modulates signaling and cellular processes in an intricate interplay with protein phosphorylation and serves as a key sensor of nutrients by linking the hexosamine biosynthetic pathway to cellular signaling. A longstanding conundrum has been how yeast survives without O-GlcNAcylation in light of its similar phosphorylation signaling system. We previously developed a sensitive lectin enrichment and mass spectrometry workflow for identification of the human O-linked mannose (O-Man) glycoproteome and used this to identify a pleothora of O-Man glycoproteins in human cell lines including the large family of cadherins and protocadherins. Here, we applied the workflow to yeast with the aim to characterize the yeast O-Man glycoproteome, and in doing so, we discovered hitherto unknown O-Man glycosites on nuclear, cytoplasmic, and mitochondrial proteins in S. cerevisiae and S. pombe. Such O-Man glycoproteins were not found in our analysis of human cell lines. However, the type of yeast O-Man nucleocytoplasmic proteins and the localization of identified O-Man residues mirror that of the O-GlcNAc glycoproteome found in other eukaryotic cells, indicating that the two different types of O-glycosylations serve the same important biological functions. The discovery opens for exploration of the enzymatic machinery that is predicted to regulate the nucleocytoplasmic O-Man glycosylations. It is likely that manipulation of this type of O-Man glycosylation will have wide applications for yeast bioprocessing.

scholarly journals The Orb6-Sts5 Axis Regulates Stress Granule Formation and Heat Stress Response in Fission Yeast

2021 ◽  
Author(s):  
Robert N. Tams ◽  
Chuan Chen ◽  
Illyce Nuñez ◽  
Patrick Roman Haller ◽  
Fulvia Verde
Keyword(s):  
Heat Stress ◽  
Cell Growth ◽  
Cell Survival ◽  
Rna Binding ◽  
Stress Granules ◽  
Stress Granule ◽  
Granule Formation ◽  
Heat Stress Response ◽  
P Bodies ◽  
Intrinsically Disordered

AbstractThe NDR/LATS family kinases are a subclass of the AGC serine/threonine kinases which are important for morphogenesis and cell growth control. Using the model organismSchizosaccharomyces pombe, we previously reported that the NDR/LATS kinase Orb6 phosphorylates the RNA-binding protein (RBP) Sts5 serine 86 residue on its Intrinsically Disordered Domain (IDD). When dephosphorylated, Sts5 forms ribonucleoprotein (RNP) granules that colocalize with processing bodies (P-Bodies) and translationally repress mRNAs important for polarized cell growth. Here we report that Sts5 puncta colocalize with both P-Bodies and stress granules (SG) in response to glucose starvation, as well as heat, oxidative, and hyperosmotic stress. We find that loss of Sts5 decreases the number of stress granules, indicating that Sts5 has a role in promoting stress granule formation. Conversely, inhibition of Orb6 kinase promotes Sts5 aggregation and stress granule formation. In addition, loss of Sts5 decreases cell survival after heat stress, whereas decreasing Orb6 protein levels or including thests5S86Amutation, which promotes Sts5 aggregation, leads to increased survival. These data indicate that the Orb6-Sts5 axis is not only important for regulation of polarized growth but also for response to environmental stress, as dysregulation of the Orb6-Sts5 axis affects stress granule formation and cell survival.

scholarly journals Musashi-1 maintains blood–testis barrier structure during spermatogenesis and regulates stress granule formation upon heat stress

2015 ◽  
Vol 26 (10) ◽  
pp. 1947-1956 ◽  
Author(s):  
Sun ErLin ◽  
Wei WenJie ◽  
Wang LiNing ◽  
Lu BingXin ◽  
Lei MingDe ◽  
...  
Keyword(s):  
Heat Stress ◽  
Cell Fate ◽  
Sertoli Cell ◽  
Sertoli Cells ◽  
Stress Granules ◽  
Stress Granule ◽  
Granule Formation ◽  
Associated Proteins ◽  
Blood Testis Barrier

In mouse testes, Musashi-1 (Msi-1) was predominantly expressed in the cytoplasm and nuclei of Sertoli cells. Here we demonstrate that knockdown of Msi-1 in Sertoli cells altered the levels and distribution of blood–testis barrier (BTB)-associated proteins. Moreover, Msi-1 knockdown in vivo disrupted BTB functional structure and spermatogenesis. In addition, we report a novel role of Msi-1 in regulating Sertoli cells survival following heat-induced injury. Endogenous Msi-1 protein in heat-treated Sertoli cells was recruited to stress granules. The formation of stress granules was considerably disrupted, and apoptosis was significantly up-regulated in Msi-1–knockdown Sertoli cells after heat treatment. p-ERK1/2 acted downstream of stress granule formation, and inhibition of p-ERK1/2 signaling triggered Sertoli cell apoptosis upon heat stress. In conclusion, we demonstrate that Msi-1 is critical for constructing a functional BTB structure and maintaining spermatogenesis. We also note a role for Msi-1 in regulating Sertoli cell fate following heat-induced injury, likely through the induction of stress granule formation and subsequent activation of p-ERK1/2 signaling.

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